Differential immunodominance hierarchy of CD8+ T-cell responses in HLA-B*27: 05- and -B*27:02-mediated control of HIV-1 infection

Emily Adland; Matilda Hill; Nora Lavandier; Anna Csala; Anne Edwards; Fabian Chen; Marek Radkowski; Justyna D. Kowalska; Dimitrios Paraskevis; Angelos Hatzakis; Humberto Valenzuela-Ponce; Katja Pfafferott; Ian Williams; Pierre Pellegrino; Persephone Borrow; Masahiko Mori; Jürgen Rockstroh; Julia G. Prado; Beatriz Mothe; Judith Dalmau; Javier Martinez-Picado; Gareth Tudor-Williams; John Frater; Anette Stryhn; Soren Buus; Gustavo Reyes Teran; Simon Mallal; Mina John; Susan Buchbinder; Gregory Kirk; Jeffrey Martin; Nelson Michael; Jacques Fellay; Steve Deeks; Bruce Walker; Santiago Avila-Rios; David Cole; Christian Brander; Mary Carrington; Philip Goulder

doi:10.1128/JVI.01685-17

Differential immunodominance hierarchy of CD8⁺ T-cell responses in HLA-B27: 05- and -B27:02-mediated control of HIV-1 infection

Emily Adland, Matilda Hill, Nora Lavandier, Anna Csala, Anne Edwards, Fabian Chen, Marek Radkowski, Justyna D. Kowalska, Dimitrios Paraskevis, Angelos Hatzakis, Humberto Valenzuela-Ponce, Katja Pfafferott, Ian Williams, Pierre Pellegrino, Persephone Borrow, Masahiko Mori, Jürgen Rockstroh, Julia G. Prado, Beatriz Mothe, Judith DalmauJavier Martinez-Picado, Gareth Tudor-Williams, John Frater, Anette Stryhn, Soren Buus, Gustavo Reyes Teran, Simon Mallal, Mina John, Susan Buchbinder, Gregory Kirk, Jeffrey Martin, Nelson Michael, Jacques Fellay, Steve Deeks, Bruce Walker, Santiago Avila-Rios, David Cole, Christian Brander, Mary Carrington, Philip Goulder^*

^*Corresponding author af dette arbejde

6 Citationer (Scopus)

125 Downloads (Pure)

Abstract

The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05- restricted CD8⁺ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8⁺ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLAB* 27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02- restricted CD8⁺ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8⁺ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLAB* 27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8⁺ T-cell responses that dominate HIV-specific CD8⁺ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.

Originalsprog	Engelsk
Artikelnummer	e01685-17
Tidsskrift	Journal of Virology
Vol/bind	92
Udgave nummer	4
Antal sider	14
ISSN	0022-538X
DOI	https://doi.org/10.1128/JVI.01685-17
Status	Udgivet - feb. 2018

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10.1128/JVI.01685-17Licens: CC BY

Differential Immunodominance Hierarchy of CD8+ T-Cell Responses in HLA-B*27:05- and -B*27:02-Mediated Control of HIV-1 InfectionForlagets udgivne version, 1,99 MBLicens: CC BY

Citationsformater

Adland, E., Hill, M., Lavandier, N., Csala, A., Edwards, A., Chen, F., Radkowski, M., Kowalska, J. D., Paraskevis, D., Hatzakis, A., Valenzuela-Ponce, H., Pfafferott, K., Williams, I., Pellegrino, P., Borrow, P., Mori, M., Rockstroh, J., Prado, J. G., Mothe, B., ... Goulder, P. (2018). Differential immunodominance hierarchy of CD8⁺ T-cell responses in HLA-B*27: 05- and -B*27:02-mediated control of HIV-1 infection. Journal of Virology, 92(4), Artikel e01685-17. https://doi.org/10.1128/JVI.01685-17

Adland, E, Hill, M, Lavandier, N, Csala, A, Edwards, A, Chen, F, Radkowski, M, Kowalska, JD, Paraskevis, D, Hatzakis, A, Valenzuela-Ponce, H, Pfafferott, K, Williams, I, Pellegrino, P, Borrow, P, Mori, M, Rockstroh, J, Prado, JG, Mothe, B, Dalmau, J, Martinez-Picado, J, Tudor-Williams, G, Frater, J, Stryhn, A , Buus, S, Teran, GR, Mallal, S, John, M, Buchbinder, S, Kirk, G, Martin, J, Michael, N, Fellay, J, Deeks, S, Walker, B, Avila-Rios, S, Cole, D, Brander, C, Carrington, M & Goulder, P 2018, 'Differential immunodominance hierarchy of CD8⁺ T-cell responses in HLA-B*27: 05- and -B*27:02-mediated control of HIV-1 infection', Journal of Virology, bind 92, nr. 4, e01685-17. https://doi.org/10.1128/JVI.01685-17

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title = "Differential immunodominance hierarchy of CD8+ T-cell responses in HLA-B*27: 05- and -B*27:02-mediated control of HIV-1 infection",

abstract = "The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05- restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLAB* 27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02- restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLAB* 27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.",

keywords = "CD8 T cell, HIV Gag, HIV Nef, HLA, HLA-B*27, Human immunodeficiency virus",

author = "Emily Adland and Matilda Hill and Nora Lavandier and Anna Csala and Anne Edwards and Fabian Chen and Marek Radkowski and Kowalska, {Justyna D.} and Dimitrios Paraskevis and Angelos Hatzakis and Humberto Valenzuela-Ponce and Katja Pfafferott and Ian Williams and Pierre Pellegrino and Persephone Borrow and Masahiko Mori and J{\"u}rgen Rockstroh and Prado, {Julia G.} and Beatriz Mothe and Judith Dalmau and Javier Martinez-Picado and Gareth Tudor-Williams and John Frater and Anette Stryhn and Soren Buus and Teran, {Gustavo Reyes} and Simon Mallal and Mina John and Susan Buchbinder and Gregory Kirk and Jeffrey Martin and Nelson Michael and Jacques Fellay and Steve Deeks and Bruce Walker and Santiago Avila-Rios and David Cole and Christian Brander and Mary Carrington and Philip Goulder",

year = "2018",

month = feb,

doi = "10.1128/JVI.01685-17",

language = "English",

volume = "92",

journal = "Journal of Virology",

issn = "0022-538X",

publisher = "American Society for Microbiology",

number = "4",

}

TY - JOUR

T1 - Differential immunodominance hierarchy of CD8+ T-cell responses in HLA-B*27

T2 - 05- and -B*27:02-mediated control of HIV-1 infection

AU - Adland, Emily

AU - Hill, Matilda

AU - Lavandier, Nora

AU - Csala, Anna

AU - Edwards, Anne

AU - Chen, Fabian

AU - Radkowski, Marek

AU - Kowalska, Justyna D.

AU - Paraskevis, Dimitrios

AU - Hatzakis, Angelos

AU - Valenzuela-Ponce, Humberto

AU - Pfafferott, Katja

AU - Williams, Ian

AU - Pellegrino, Pierre

AU - Borrow, Persephone

AU - Mori, Masahiko

AU - Rockstroh, Jürgen

AU - Prado, Julia G.

AU - Mothe, Beatriz

AU - Dalmau, Judith

AU - Martinez-Picado, Javier

AU - Tudor-Williams, Gareth

AU - Frater, John

AU - Stryhn, Anette

AU - Buus, Soren

AU - Teran, Gustavo Reyes

AU - Mallal, Simon

AU - John, Mina

AU - Buchbinder, Susan

AU - Kirk, Gregory

AU - Martin, Jeffrey

AU - Michael, Nelson

AU - Fellay, Jacques

AU - Deeks, Steve

AU - Walker, Bruce

AU - Avila-Rios, Santiago

AU - Cole, David

AU - Brander, Christian

AU - Carrington, Mary

AU - Goulder, Philip

PY - 2018/2

Y1 - 2018/2

N2 - The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05- restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLAB* 27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02- restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLAB* 27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.

AB - The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05- restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLAB* 27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02- restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLAB* 27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.

KW - CD8 T cell

KW - HIV Gag

KW - HIV Nef

KW - HLA

KW - HLA-B27

KW - Human immunodeficiency virus

U2 - 10.1128/JVI.01685-17

DO - 10.1128/JVI.01685-17

M3 - Journal article

C2 - 29167337

AN - SCOPUS:85041231839

SN - 0022-538X

VL - 92

JO - Journal of Virology

JF - Journal of Virology

IS - 4

M1 - e01685-17

ER -